Infectious Diseases Flashcards
Note:
Aerobic bacteria require oxygen whereas anaerobic bacteria do not. GRAM POSITIVE bacteria have a thick peptidoglycan cell wall that stains with crystal violet stain. GRAM NEGATIVE bacteria don’t have this thick peptidoglycan cell wall and don’t stain with crystal violet stain will stain with other stains. ATYPICAL BACTERIA cannot be stained or cultured in the normal way.
Also rod shaped bacteria are called bacilli and circular shaped bacteria are called cocci.
Note:
Nucleic acid is an essential component of bacterial DNA
Ribosomes are where bacteria proteins are synthesised within the bacterial cell.
Folic acid is essential for the synthesis and regulation of DNA within the bacteria. Folic acid cannot be directly imported into the cell and requires a chain of intermediates to get in. This chain starts with para-aminobenzoic acid (PABA), which is directly absorbed across the cell membrane and into the cell. PABA is converted to dihydrofolic acid (DHFA), which is converted inside the cell to tetrahydrofolic acid (THFA), then folic acid.
Note:
A gram stain is used as a quick way to check a sample under a microscope to look for bacteria. It involves two main steps:
Add a crystal violet stain, which binds to molecules in the thick peptidoglycan cell wall in gram positive bacteria turning them violet.
Then add a counterstain (such as safranin) which binds to the cell membrane in bacteria that don’t have a thick, peptidoglycan cell wall (gram negative bacteria) turning them red/pink
Gram positive cocci ?
Staphylococcus
Streptococcus
Enterococcus
Gram positive rods ?
Use the mnemonic “corney Mike’s list of basic cars”:
Corney - Corneybacteria Mike's - Mycobacteria List of - Listeria Basic - Bacillus Cars - Nocardia
Gram positive anaerobes ?
CLAP
C - Clostridium
L - Lactobacillus
A - Actinomyces
P - Propionibacterium
Gram negative bacteria ?
Neisseria meningitidis Neisseria gonorrhoea Hameophilia influenza E. coli Klebsiella Pseudomonas aeruginosa Moraxella catarrhalis
Definition of an atypical bacteria ?
Bacteria that cannot be cultured in the normal way or detected using a gram stain.
Atypical are most often implicated in what ?
Pneumonia
Atypical bacteria that cause atypical pneumonia ?
“Legions of psittaci MCQs”
Legions - Legionella pneumophila Psittaci - Chlamydia psittaci M - Mycoplasma pneumoniae C - Chlamydophilia pneumoniae Qs - Q fever (coxiella burnetii)
Which type of antibiotics is MRSA resistant to + give examples?
Beta-lactam antibiotics such as penicillins, cephalosporins and carbapenems.
People are often colonised with MRSA bacteria and have them living harmlessly on their skin and respiratory tract. If these bacteria become part of an infection they can be difficult to treat. Pts being admitted for surgery or inpatient treatment are screened for MRSA infection by taking nose and groin swabs, so that extra measures can be taken to try and eradicate them and stop their spread. Eradication involves a combination of what ?
Chlorhexidine body washes and antibacterial nasal creams
Antibiotic treatment options for MRSA are ?
Doxycycline Clindamycin Vancomycin Teicoplanin Linezolid
What are extended spectrum beta lactamase bacteria (ESBLs) ?
Bacteria that have developed resistance to beta-lactam antibiotics. They produce beta lactamase enzymes that destroy the beta-lactam ring on the antibiotic. They can be resistant to a very broad range of antibiotics.
ESBLs tend to be + what do they usually cause
E. coli or klebsiella and typically cause UTIs but can also cause other infections such as pneumonia
What are ESBLs sensitive to ?
Carbapenems such as meropenem or imipenem.
What do bacteriostatic antibiotics do ?
They either stop the reproduction or growth of bacteria
What do bactericidal antibiotics do ?
They directly kill bacteria
TOM TIP:
In your OSCEs questions about treating infections can always be answered with “treat with antibiotics according to the local antibiotic policy”
Antibiotics that inhibit cell wall synthesis ?
Antibiotics with a beta-lactam ring:
- Penicillin
- Carbapenems such as meropenem
- Cephalosporins
Antibiotics without a beta-lactam ring:
- Vancomycin
- Teicoplanin
Antibiotics that inhibit folic acid metabolism ?
- Sulfamethoxazole blocks the conversion of DHFA to THFA
- Trimethoprim blocks the conversion of THFA to folic acid
-Co-trimoxazole is a combination of the two.
Metronidazole ?
The reduction of metronidazole into its active form only occurs in anaerobic cells. When partially reduced, metronidazole inhibits nucleic acid synthesis
Antibiotics that inhibit protein synthesis by targeting the ribosome ?
- Macrolides such as erythromycin, clarithromycin and azithromycin
- Clindamycin
- Tetracyclines such as doxycycline
- Gentamicin
- Chloramphenicol
TOM TIP:
When taking an allergy history always ask what reaction pts have with that medication. If they report diarrhoea for example, this is a side effect rather than an allergy and means if necessary (for example in life threatening sepsis) they can still receive that medication
Stepwise process of escalating antibiotic treatment ?
Start with AMOXICILLIN which covers streptococcus, listeria and enterococcus
Switch to CO-AMOXICLAV to additionally cover staphylococcus, haemophilus and e. coli
Switch to TAZOCIN to additionally cover pseudomonas
Switch to MEROPENEM to additionally cover ESBLs
Add TEICOPLANIN or VANCOMYCIN to cover MRSA
Add CLARITHROMYCIN or DOXYCYCLINE to cover atypical bacteria
What is sepsis ?
A condition where the body launches a large immune response to an infection that causes systemic inflammation and affects organ function
Pathophysiology of sepsis ?
Pathogens are recognised by macrophages, lymphocytes and mast cells. These cells release vast amounts of cytokines like interleukins and tumour necrosis factor to alert the immune system to the invader. These cytokines activate other parts of the immune system. This immune activation leads to further release of chemicals such as nitrous oxide that causes vasodilation. The immune response causes inflammation throughout the body.
Many of these cytokines cause the endothelial lining of blood vessels to become more permeable. This causes fluid to leak out of the blood into the extracellular space, leading to oedema and a reduction in intravascular volume. The oedema around blood vessels creates a space between the blood and the tissues, reducing the amount of oxygen that reaches the tissues.
Activation of the coagulation system leads to deposition of fibrin throughout the circulation, further compromising organ and tissue perfusion. It also leads to consumption of platelets and clotting factors as they are being used up to form the clots. This leads to thrombocytopenia, haemorrhages and an inability to form clots and stop bleeding. This is called disseminated intravascular coagulopathy (DIC).
Blood lactate rises due to anaerobic respiration in the hypo-perfused tissues with inadequate oxygen. A waste product of anaerobic respiration is lactate.
What is septic shock ?
It is defined when arterial blood pressure drops resulting in organ hypo-perfusion. This leads to a rise in blood lactate as the organs begin anaerobic respiration. This can be measured as either:
- Systolic blood pressure less than 90 despite fluid resuscitation
- Hyperlactaemia (lactate > 4 mmol/L)
Management of septic shock ?
Should be treated aggressively with IV fluids to improve the BP and tissue perfusion. If IV fluid boluses don’t improve the BP and lactate level the pt should be escalated to the HDU or ICU where they can use inotropes (such as noradrenaline) that help stimulate the CVS and improve BP and tissue perfusion.
What is severe sepsis ?
It is defined as when sepsis is present and results in organ dysfunction, for example:
- Hypoxia
- Oliguria
- AKI
- Thrombocytopenia
- Coagulation dysfunction
- Hypotension
- Hyperlactaemia (>2 mmol/L)
Risk factors for sepsis ?
Any condition that impacts the immune system or makes the pt more frail or prone to infection is a risk factor for developing sepsis:
- Very young or old pts (under 1 or over 75 years)
- Chronic conditions such as COPD and diabetes
- Chemotherapy, immunosuppressants or steroids
- Surgery, recent trauma or burns
- Pregnancy or peripartum
- Indwelling medical devices such as catheters or central lines
Presentation of sepsis ?
The national early warning score (NEWS) is used in the UK to pick up the signs of sepsis. This involves checking physical observations and consciousness level:
- Temperature
- Heart rate
- Respiratory rate
- Oxygen sats
- BP
- Consciousness level
Other signs on examination that could indicate sepsis ?
- Signs of potential sources such as cellulitis, discharge from a wound, cough or dysuria
- Non-blanching rash can indicate meningococcal septicaemia
- Reduced urine output
- Mottled skin
- Cyanosis
- Arrhythmias such as new onset atrial fibrillation
Key points to be aware of in regards to the presentation of sepsis ?
- Tachypnoea is often the first sign of sepsis
- Elderly pts often present with confusion, drowsiness or simply “off legs”
- Neutropenic or immunosuppressed pts may have normal observations and temperature despite being life threateningly unwell
Investigations for sepsis (include possible extra investigations)?
Arrange blood tests for pts with suspected sepsis:
- FBC - to assess cell count including white cells and neutrophils
- U&Es - to assess kidney function and look for AKI
- LFTs to assess liver function and for possible source of infection
- CRP - to assess inflammation
- Clotting - to assess for DIC
- Blood cultures to assess for bacteraemia
- Blood gas to assess lactate, pH and glucose
Additional investigations that can be helpful in locating the source of the infection:
- Urine dipstick and culture
- CXR
- CT scan if intra-abdominal infection or abscess is suspected
- Lumbar puncture for meningitis or encephalitis
Septic pts should be assessed and have treatment initiated within 1 hour of presenting with suspected sepsis. This involves performing the sepsis six, what is this ?
BUFALO
B - Blood cultures U - Urine output F - IV fluids A - Empirical broad spectrum (A)ntibiotics L - Blood (L)actate level O - Oxygen
What is neutropenic sepsis ?
A very important medical emergency. It is sepsis in pts with a low neutrophil count of less than 1 x 10(to the power of 9)/L
Neutropenia is usually the consequence of anti-cancer or immunosuppressant treatment. Name some medications that may cause neutropenia ?
- Anti cancer chemotherapy
- Clozapine (schizophrenia)
- Hydroxychloroquine (rheumatoid arthritis)
- Methotrexate (RA)
- Sulfasalazine (RA)
- Carbimazole (hyperthyroidism)
- Quinine (malaria)
- Infliximab (monoclonal antibody use for immunosuppression)
- Rituximab (monoclonal antibody use for immunosuppression)
Note:
Have a low threshold for suspecting neutropenic sepsis in pts taking immunosuppressants or medications that may cause neutropenia. Treat any temperature above 38°C as neutropenic sepsis in these pts until proven otherwise. They are at high risk of death from sepsis as their immune system cannot adequately fight the infection. They need emergency admission and careful management.
Each local hospital treatment will have a neutropenic sepsis policy. Treatment is with what (include an example)
Immediate broad spectrum antibiotics such as piperacillin with tazobactam (tazocin).
The other aspects of management are essentially the same as for sepsis, however extra precaution needs to be taken. Time is precious so don’t delay antibiotics while waiting for investigation results.
Antibiotic choice for chest infections in the community ?(include initial antibiotics, alternatives and what you would use to treat atypical bacteria)
An appropriate initial antibiotic in the community would be:
-Amoxicillin
Alternatives
- Erythromycin/ clarithromycin
- Doxycycline
To treat atypical bacteria:
- Macrolides such as clarithromycin
- Quinolones such a levofloxacin
- Tetracyclines such as doxycycline
Note:
The main source of bacteria for UTIs is from the faeces, where the normal intestinal bacteria such as E. coli can easily make the short journey to the urethral opening from the anus. Sexual activity is a key method for spreading bacteria around the perineum. They are also very common in women where incontinence or hygiene are a problem.
Urinary catheters are a key source of infection and catheter associated UTIs tend to be more significant and difficult to treat.
Presentation of a lower UTI ?
- Dysuria
- Suprapubic pain or discomfort
- Frequency
- Urgency
- Incontinence
- Confusion is commonly the only symptom in older more frail pts
Presentation of pyelonephritis ?
- Fever
- Loin, suprapubic or back pain. This may be bilateral or unilateral
- Looking and feeling generally unwell
- Vomiting
- Loss of appetite
- Haematuria
- Renal angle tenderness on examination
Urine dipstick note (relating to UTIs):
Nitrites - gram negative bacteria (such a E. coli) break down nitrates, a normal waste product in urine, into nitrites. The presence of nitrites suggest bacteria in the urine.
Leukocytes - There are normally a small number of leukocytes in the urine but a significant rise can be the result of an infection or other cause of inflammation. Urine dipsticks test for leukocyte esterase, a product of leukocytes that gives an indication to the number of leukocytes in the urine.
NITRITES are a better indication of infection than LEUKOCYTES. If both are present the pt should be treated as a UTI. If only NITRITES are present it is worth treating as a UTI. If only leukocytes are present the pt should not be treated as a UTI unless there is clinical evidence they have one.
If nitrites or leukocytes are present, the urine should be sent to the microbiology lab. If neither are present the pt is unlikely to have a UTI.
Send a MSU sample to the microbiology lab to be cultured and have sensitivity testing.
Most common cause of UTIs + other causes ?
Most common cause is E. coli. This is a gram negative, anaerobic baccilus that is part of the normal lower intestinal microbiome. It is found in faeces and can easily spread to the bladder.
Other causes:
- Klebsiella pneumoniae (gram negative anaerobic rod)
- Enterococcus
- Pseudomonas aeruginosa
- Staphylococcus saprophyticus
- Candida albicans (fungal)
Antibiotic choice for a UTI ?
An appropriate initial antibiotic in the community would be:
- Trimethoprim
- Nitrofurantoin
Alternatives:
- Pivmecillinam
- Amoxicillin
- Cefalexin
Duration of antibiotics for a UTI ?
- 3 DAYS of antibiotics for a simple lower UTI in women
- 5-10 DAYS of antibiotics for women that are immunosuppressed, have abnormal anatomy or impaired kidney function
- 7 DAYS of antibiotics for men, pregnant women or catheter related UTIs
It is worth noting that NICE recommend changing the catheter when someone is diagnosed with a catheter related urinary tract infection
UTIs in pregnancy increase the risk of pyelonephritis, PROM and pre-term labour. How are UTIs managed in pregnancy + when are nitrofurantoin and trimethoprim avoided ?
- 7 days of antibiotics (even with asymptomatic bacteriauria)
- Urine for culture and sensitivities
- First line: nitrofurantoin
- Second line: cefalexin or amoxicillin
Nitrofurantoin is generally avoided in the third trimester as it is linked with haemolytic anaemia in the newborn.
Trimethoprim is generally considered safe in pregnancy but avoided in the first trimester or if they are on another medication that affects folic acid (such as anti-epileptics) due to the anti-folate effects.
Management of pyelonephritis ?
Referral to hospital if there are features of sepsis
NICE recommend following first line antibiotics for 7-10 days when treating pyelonephritis in the community:
- Cefalexin
- Co-amoxiclav
- Trimethoprim
- Ciprofloxacin
What is cellulitis ?
An bacterial infection of the dermis and subcutaneous fat.
When a pt presents with cellulitis you should look for what + what could this be due to ?
A breach in the skin barrier and a point of entry for the bacteria.
This may be due to skin trauma, eczematous skin, fungal nail infections or ulcers.
Presentation of cellulitis ?
- Erythema (red discolouration)
- Warm or hot to touch
- Tense
- Thickened
- Oedematous
- Bullae (fluid filled blisters)
- A golden-yellow curst can be present and indicates a staphylococcus aureus infection
Causes of cellulitis ?
Most common causes are:
- Staph aureus
- Group A streptococcus (mainly strep pyogenes)
- Group C streptococcus (mainly strep dysgalactiae)
MRSA is another cause that needs to be considered
Assessment of the severity of cellulitis + when should pts be admitted?
Eron classification:
Class 1 - no systemic toxicity or comorbidity
Class 2 - systemic toxicity or comorbidity
Class 3 - significant systemic toxicity or significant comorbidity
Class 4 - sepsis or life threatening infection
Admit the pts for IV antibiotics if they are class 3 or 4. Also consider admission for frail, very young or immunocompromised pts
Treatment of cellulitis ?
Antibiotics:
Flucloxacillin is very effective against staph infections and also works well against other gram positive cocci. It is usually the first choice in treating cellulitis and can be give orally or IV.
Alternatives:
- Clarithromycin
- Clindamycin
- Co-amoxiclav
Bacterial tonsillitis is most commonly caused by what ?
Group A streptococcus (GAS) infections, mainly streptococcus pyogenes
Otitis media, sinusitis and tonsillitis not caused by GAS are most commonly caused by ?
Strep pneumoniae
Other causes of otitis media, sinusitis and tonsillitis ?
Haemophilus influenzae
Moraxella catarrhalis
Staph aureus
Tonsillitis is most commonly viral and does not require antibiotics. What is the Centor criteria used for ?
It is used to estimate the probability that tonsillitis is due to a bacteria infection and requires antibiotics.
What are the components of the Centor criteria and what score indicates that it is appropriate to offer the pt antibiotics ?
- Fever ≥ 38 degrees celsius
- Tonsillar exudates
- Absence of cough
- Tender anterior cervical lymph nodes
Score of 3 or more indicates it is appropriate to offer antibiotics.
Treatment if a pt scores 3 or more on Centor criteria ?
Penicillin V for a day 10 day course is typically first line.
Alternative antibiotics for a broader specrum of activity:
- Co-amoxiclav
- Clarithromycin
- Doxycycline
It is difficult to distinguish between bacterial and viral otitis media. It presents with ear pain. Examination will reveal a bulging red tympanic membrane. If the ear drum perforates there can be discharge from the ear.
Otitis media usually resolves 3 to 7 days without antibiotics. If systemically unwell consider admission.
Which antibiotics would you prescribe if appropriate ?(include initial antibiotic in the community, alternatives if penicillin allergy and second line if not responding to amoxicillin after 2 days)
An appropriate initial antibiotic in the community:
-Amoxicillin
Alternatives to penicillin:
- Clarithromycin
- Erythromycin
Second line if not responding to amoxicillin after 2 days:
-Co-amoxiclav
Sinusitis can be bacterial or viral. NICE recommend providing an antibiotic if the pt is systemically very unwell, however most pts do not require antibiotics. Sinusitis usually last 2-3 weeks and resolves without treatment.
Management of sinusitis ?
NICE guidelines suggest the following management:
- Symptoms for less than 10 days: no antibiotics
- No improvement after 10 days: 2 weeks of high-dose steroid nasal spray
- No improvement after 10 days and likely bacterial cause: consider delayed or immediate prescription antibiotics
Penicillin V for a 5 day course is typically first line. Co-amoxiclav is used second line if they do not respond after at least 2-3 days.
Alternatives:
- Clarithromycin
- Erythromycin (pregnancy)
- Doxycycline
Common causes of intra-abdominal infections ?
- Anaerobes (e.g. bacteroides and clostridium)
- E. coli
- Klebsiella
- Enterococcus
- Streptococcus
Note:
When treating intra abdominal infections a broad spectrum of antibiotic cover is required unless culture results are available. It needs to cover gram positive, gram negative and anaerobic bacteria. Always follow the local guidelines as these are frequently changed based on local resistance and infection control issues.
Antibiotics for intra-abdominal infections ?
CO-AMOXICLAV:
This provides good gram positive, gram negative and anaerobic cover. It does not cover pseudomonas or atypical bacteria.
QUINOLONES
Ciprofloxacin and levofloxacin provide reasonable gram positive and gram negative cover and also cover atypical bacteria however they don’t cover anaerobes so are usually paired with metronidazole when treating intra-abdominal infections
METRONIDAZOLE
This provides exceptional anaerobic cover but does not provide any cover against aerobic bacteria
GENTAMiCIN
This provides very good gram negative cover with some gram positive cover particularly against staphylococcus. It is bactericidal, so works to kill the bacteria rather than just slowing it down.
VANCOMYCIN
This provides very good gram positive cover including MRSA. It is often combined with gentamicin (to cover gram negatvies) and metronidazole (to cover anaerobes) in pts with penicillin allergy.
CEPHALOSPORINS
These provide good broad spectrum cover against gram positive and gram negative bacteria but are not very effective against anaerobes. They are often avoided due to the risk of developing C. difficile infection.
TAZOCIN AND MEROPENEM
Piperacillin/tazobactam (tazocin) and meropenem are heavy hitting antibiotics that cover gram positive, gram negative and anaerobic bacteria. They don’t cover atypical bacteria or MRSA and tazocin doesn’t cover ESBLs, but they cover almost everything else. They are usually reserved for very unwell pts.
Common regimes for intra-abdominal infection ?
- Co-amoxiclav alone
- Amoxicillin plus gentamicin plus metronidazole
- Ciprofloxacin plus metronidazole (penicillin allergy)
- Vancomycin plus gentamicin plus metronidazole (penicillin allergy)
Note:
Antibiotics can be given orally when an oral version is available, for example in mild diverticulitis, or IV in more serious infections.
A stat dose of GENTAMICIN is often added to regimes not including gentamicin if the pt is severely septic to provide strong initial bactericidal gram negative action.
Management of spontaneous bacterial peritonitis ?
- Piperacillin and tazobactam (tazocin) is often first line
- Cephalosporins such as cefotaxime are often used
- Levofloxacin plus metronidazole is a common alternative in penicillin allergy.
What is septic arthritis ?
When an infection occurs in a joint.
Notes:
- This can be in a native joint or in a joint replacement
- It is a medial emergency
- Has a mortality rate of around 10%
